Huberman and Sachs have described a cell-mediated mutagenesis assay for measuring the capacity of cultured diploid fibroblasts to convert polycyclic hydrocarbon carcinogens to their mutagenic metabolites. Employing their assay of cell-mediated mutagenesis with cultured diploid fibroblasts obtained from six different mammalian species of widely differing life-spans, we have found a very good inverse correlation between species life-span and apparent capacity to activate 7,12-dimethylbenz(a)anthracene (DMBA) to a mutagenic form. Our immediate objective is to confirm and extend the above observation by establishing multiple fibroblast strains from animals from a large number of mammalian species, and determine if their capacity to activate DMBA in the cell-mediated mutagenesis assay correlates inversely with species life-span. We will also determine if the above inverse correlation exists for other polycyclic hydrocarbon carcinogens, as well as for carcinogens of other classes, i.e. aflatoxin B1, etc. We plan to measure the capacity of cultured diploid fibroblasts obtained from various species to metabolize (H3)DMBA to water-soluble products, as well as to determine the level of benzo(a)pyrene hydroxylase activity in cell-free extracts of the above cultured fibroblasts.